text: From intravenous (IV) animal studies the toxic dose (LD) of palytoxin via IV for humans has been estimated by extrapolation to be between 2.3 and 31.5 micrograms (µg) of palytoxin. An acute oral reference dose has been suggested to be 64 µg for a person with weight of 60 kg. Acute reference dose means a dose that can be safely ingested over a short period of time, usually during one meal or one day.
  In comparison to IV injection, the toxicity of palytoxin in various animals via intramuscular and subcutaneous injections are 2.5 and 4–30 times higher, respectively. Upon ingestion the toxicity in animals has been 200 times less than via IV. In the table below, there are listed some LD values for partially pure palytoxin obtained from different Palythoa. These values represent the amount of palytoxin required to kill half of the test animals. Values are in micrograms (µg) per kilogram of the animal's weight and have been measured 24 hours after the initial exposure.
  An early toxicological characterization classified palytoxin as "relatively non-toxic" after intragastric administration to rats. The lethal dose (LD) was greater than 40 µg/kg. The LD after parenteral administration was lower than 1 µg/kg. However the doubtful purity of this study increased because of uncertainty concerning the toxicological data. In 1974, the structure of palytoxin was not completely elucidated and the molecular weight was a lot higher (3300 Da instead of 2681 Da). A 2004 study discovered an LD of 510 µg/kg after intragastric administration in mice, but histological or biochemical information was missing. (Rhodes and Munday, 2004) Furthermore, palytoxin was not lethal to mice given an oral dose of 200 µg/kg. It was also found that palytoxin is very toxic after intraperitoneal injection. The LD in mice was less than 1 µg/kg. Because toxin-producing organisms spread to temperate climates and palytoxin-contaminated shellfish were discovered in the Mediterranean Sea a study was done to better define the toxic effects of palytoxin after oral exposure in mice. Palytoxin was lethal from 600 µg/kg doses. The number of deaths were dose-dependent and the LD calculated to be 767 µg/kg. This is comparable to the LD of 510 µg/kg referred by Munday (2008). The toxicity was not different if the mice had some food in their stomach. The oral toxicity is several times lower than the intraperitoneal toxicity. One of the possible causes of this behavior is that palytoxin is a very big hydrophilic molecule and therefore the absorption could be less efficient through the gastrointestinal tract than through the peritoneum. A recent study by Fernandez et al. further investigated on this issue using an in vitro model of intestinal permeability with differentiated monolayers of human colonic Caco-2 cells, confirming that palytoxin was unable to cross the intestinal barrier significantly, despite the damage the toxin exerted on cells and on the integrity of the monolayer. The same study also revealed that palytoxin does not affect tight-junctions on such cells. Palytoxin is most toxic after intravenous injection. The LD in mice is 0.045 µg/kg and in rats 0.089 µg/kg. In other mammals (rabbits, dogs, monkeys and guinea pigs) the LD is ranged between 0.025 and 0.45 µg/kg. They all died in several minutes from heart failure. The lethal dose for mice by the intratracheal route is above 2 µg/kg in 2 hours. Palytoxin is also very toxic after intramuscular or subcutaneous injection. No toxicity is found after intrarectal administration. Palytoxin is not lethal when topically applied to skin or eyes. Palytoxin can travel in water vapor and cause poisoning by inhalation.
  In this context, despite an increase in reports of palytoxin contaminated seafood in temperate waters (i.e., Mediterranean Sea), there are no validated and accepted protocols for the detection and quantification of this class of biomolecules. However, in recent years, many methodologies have been described with particular attention on the development of new techniques for the ultrasensitive detection of palytoxin in real matrix such as mussels and microalgae (based on LC-MS-MS or immunoassay).